Catalysis of the Phosphorylase Kinase Activation Reaction

Abstract

Abstract Activation of skeletal muscle phosphorylase kinase, which occurs when the purified enzyme is incubated with ATP, Mg2+, and cyclic adenosine 3',5'-monophosphate (cyclic AMP), has been shown to involve two catalytic components. One of the catalysts is a cyclic AMP-dependent protein kinase and the other is phosphorylase kinase itself. The process was elucidated in part through a study of the effects of inhibitors on the activation process. One of the inhibitors that was used is a heat-stable protein from skeletal muscle which was shown to block the cyclic AMP-dependent protein kinase component of the reaction, and the other inhibitor was ethylene glycol bis(β-aminoethyl ether)-N, N'-tetraacetate which inhibits phosphorylase kinase. Clarification of the mechanisms operating at the phosphorylase kinase activation step makes it possible to describe more precisely how glycogenolysis is regulated by hormones, and for the first time to identify a specific site of action of cyclic AMP in a physiological process.